Activated caspase-9 immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy.

Abstract

The mitochondria play an important role in apoptotic cell death, and the released cytochrome c from the mitochondria promotes the formation of the apoptosome, which contains cytochrome c, Apaf-1 and caspase-9, resulting in the activation of caspase-9 and the promotion of the apoptotic cascade. To investigate the role of mitochondria-dependent apoptotic cell death in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on apoptosome-related proteins in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. We then performed double-labeling immunohistochemistry for activated caspase-9 and α-synuclein in some sections from 10 patients with MSA. In the brains with MSA, glial cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs) were intensely immunoreactive for cytochrome c, Apaf-1 and caspase-9. Activated caspase-9 immunoreactivities were also confirmed to be densely localized to both GCIs and NCIs using two types of anti-cleaved caspase-9 antibodies. The semiquantitative analyses using the upper pontine sections double-immunostained with cleaved caspase-9 and α-synuclein demonstrated that approximately 80% of GCIs and NCIs were immunopositive for cleaved caspase-9. Our results suggest that the formation of the apoptosome accompanied by the activation of caspase-9 may occur in brains affected by MSA, and that a mitochondria-dependent apoptotic pathway may be partially associated with the pathogenesis of MSA.

• Authors: Yasuhiro Kawamoto, Takashi Ayaki, Makoto Urushitani, Hidefumi Ito, Ryosuke Takahashi
• Journal: Neuroscience letters (Neurosci Lett) Vol. 628 Pg. 207-12 (08 15 2016) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 27345387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• APAF1 protein, human
• Apoptotic Protease-Activating Factor 1
• Cytochromes c
• Caspase 9

Topics

• Aged
• Apoptosis
• Apoptotic Protease-Activating Factor 1 (metabolism)
• Brain (enzymology, pathology)
• Caspase 9 (metabolism)
• Cytochromes c (metabolism)
• Female
• Humans
• Inclusion Bodies (enzymology)
• Male
• Middle Aged
• Multiple System Atrophy (enzymology, pathology)
• Neuroglia (enzymology, pathology)
• Neurons (enzymology, pathology)